Neuroinflammation

Neuroinflammation refers to the inflammatory response within the central nervous system, primarily mediated by microglia (the brain's resident immune cells) and astrocytes (support cells with immune functions). Unlike peripheral inflammation, which involves circulating white blood cells, the brain's immune response is conducted largely by cells that normally reside in brain tissue.

Acute neuroinflammation is a protective response: microglia detect pathogens, cellular debris, and abnormal protein aggregates and respond by engulfing and degrading them. This is an essential maintenance function. Chronic neuroinflammation — when microglial activation persists — is a different matter. Chronically activated microglia release inflammatory cytokines, reactive oxygen species, and other mediators that damage neurons and synapses over time.

Neuroinflammation is now recognized as a major contributor to Alzheimer's disease pathology, not merely a consequence of it. Amyloid plaques activate microglia, but microglial activation in turn appears to promote tau pathology and neurodegeneration. Genetic risk factors for Alzheimer's — including variants in TREM2, CR1, and CLU — are expressed on microglia, reinforcing the importance of the innate immune system in Alzheimer's biology.

Peripheral inflammation — systemic inflammatory states from chronic disease, obesity, periodontitis, and other sources — appears to drive neuroinflammation through multiple pathways, including cytokines crossing the blood-brain barrier and triggering microglial activation. This is one mechanism through which conditions like obesity, type 2 diabetes, and chronic stress are associated with elevated dementia risk.

Anti-inflammatory approaches to Alzheimer's prevention have shown mixed results in clinical trials, partly because inflammation plays both protective and harmful roles — too little microglial activity impairs amyloid clearance, while too much causes collateral neuronal damage. The goal is appropriately regulated microglial function, not simply suppressed inflammation.

Diet, exercise, and sleep all modulate neuroinflammatory tone. The Mediterranean diet in particular has well-documented anti-inflammatory effects that may contribute to its association with cognitive health. Regular aerobic exercise reduces pro-inflammatory cytokine levels systemically and in the brain. Sleep deprivation, conversely, increases microglial activation and neuroinflammatory markers.